Also in this region, a locus tagged by rs578776 and rs3743078 is significantly associated with nicotine dependence and smoking in European-descent samples [10, 12, 14, 16]. This locus has been described as protective because the minor allele is more frequent in controls than in cases. There is evidence that this locus is statistically distinct from rs16969968: in two independent European-ancestry samples the correlation between rs578776 and rs16969968 is low (r2 = 0.2), with D′ = −1.0 indicating repulsion phase (the minor allele at one locus co-occurs with the major allele at the other), and both SNPs are significant in joint analyses [14, 20].
